The potential of desferrioxamine-gallium as an anti-Pseudomonas therapeutic agent.
The opportunistic pathogen Pseudomonas aeruginosa causes infections that are difficult to treat by antibiotic therapy. This bacterium can cause biofilm infections where it shows tolerance to antibiotics. Here we report the novel use of a metallo-complex, desferrioxamine-gallium (DFO-Ga) that targets P. aeruginosa iron metabolism. This complex kills free-living bacteria and blocks biofilm formation. A combination of DFO-Ga and the anti-Pseudomonas antibiotic gentamicin caused massive killing of P. aeruginosa cells in mature biofilms. In a P. aeruginosa rabbit corneal infection, topical administration of DFO-Ga together with gentamicin decreased both infiltrate and final scar size by about 50% compared to topical application of gentamicin alone. The use of DFO-Ga as a Trojan horse delivery system that interferes with iron metabolism shows promise as a treatment for P. aeruginosa infections.
Banin
Ehud
E
Department of Microbiology, School of Medicine, University of Washington, Seattle, WA 98195, USA.
Lozinski
Alina
A
Brady
Keith M
KM
Berenshtein
Eduard
E
Butterfield
Phillip W
PW
Moshe
Maya
M
Chevion
Mordechai
M
Greenberg
Everett Peter
EP
Banin
Eyal
E
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use; D018441:Biofilms / Q000187:drug effects; D003676:Deferoxamine / Q000494:pharmacology / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D015818:Eye Infections, Bacterial / Q000188:drug therapy; D005708:Gallium; D005839:Gentamicins / Q000494:pharmacology / Q000627:therapeutic use; D007501:Iron / Q000378:metabolism; D011552:Pseudomonas Infections / Q000188:drug therapy*; D011550:Pseudomonas aeruginosa / Q000187:drug effects*; D011817:Rabbits; D016896:Treatment Outcome
D000900:Anti-Bacterial Agents; D005839:Gentamicins; D005708:Gallium; D007501:Iron; D003676:Deferoxamine